1. Field of the Invention
The present invention relates generally to apparatus and methods for inhibiting restenosis in arteries following angioplasty or other intravascular procedures for treating atherosclerotic disease. More particularly, the present invention relates to apparatus and methods for cryogenically treating the target site within a patient""s vasculature to inhibit hyperplasia which can occur after such intravascular procedures.
A number of percutaneous intravascular procedures have been developed for treating atherosclerotic disease in a patient""s vasculature. The most successful of these treatments is percutaneous transluminal angioplasty (PTA) which employs a catheter having an expansible distal end, usually in the form of an inflatable balloon, to dilate a stenotic region in the vasculature to restore adequate blood flow beyond the stenosis. Other procedures for opening stenotic regions include directional arthrectomy, rotational arthrectomy, laser angioplasty, stents and the like. While these procedures, particularly PTA, have gained wide acceptance, they continue to suffer from the subsequent occurrence of restenosis.
Restenosis refers to the re-narrowing of an artery within weeks or months following an initially successful angioplasty or other primary treatment. Restenosis afflicts up to 50% of all angioplasty patients and results at least in part from smooth muscle cell proliferation in response to the injury caused by the primary treatment, generally referred to as xe2x80x9chyperplasia.xe2x80x9d Blood vessels in which significant restenosis occur will require further treatment.
A number of strategies have been proposed to treat hyperplasia and reduce restenosis. Such strategies include prolonged balloon inflation, treatment of the blood vessel with a heated balloon, treatment of the blood vessel with radiation, the administration of anti-thrombotic drugs following the primary treatment, stenting of the region following the primary treatment, and the like. While enjoying different levels of success, no one of these procedures has proven to be entirely successful in treating all occurrences of restenosis and hyperplasia.
For these reasons, it would be desirable to provide additional apparatus and methods suitable for the treatment of restenosis and hyperplasia in blood vessels. It would be further desirable if the apparatus and methods were suitable for treatment of other conditions related to excessive cell proliferation, including neoplasms resulting from tumor growth, hyperplasia in other body lumens, and the like. The apparatus and method should be suitable for intravascular and intraluminal introduction, preferably via percutaneous access. It would be particularly desirable if the methods and apparatus were able to deliver the treatment in a very focused and specific manner with minimal effect on adjacent tissues. Such apparatus and methods should further be effective in inhibiting hyperplasia and/or neoplasia in the target tissue with minimum side affects. At least some of these objectives will be met by the invention described hereinafter.
2. Description of the Background Art
Balloon catheters for intravascularly cooling or heating a patient are described in U.S. Pat. No. 5,486,208 and WO 91/05528. A cryosurgical probe with an inflatable bladder for performing intrauterine ablation is described in U.S. Pat. No. 5,501,681. Cryosurgical probes relying on Joule-Thomson cooling are described in U.S. Pat. Nos. 5,275,595; 5,190,539; 5,147,355; 5,078,713; and 3,901,241. Catheters with heated balloons for post-angioplasty and other treatments are described in U.S. Pat. Nos. 5,196,024; 5,191,883; 5,151,100; 5,106,360; 5,092,841; 5,041,089; 5,019,075; and 4,754,752. Cryogenic fluid sources are described in U.S. Pat. Nos. 5,644,502; 5,617,739; and 4,336,691.
The full disclosures of each of the above U.S. Patents are incorporated herein by reference.
The present invention comprises the cryosurgical treatment of a target site within the body lumen of a patient, usually in an artery which has been previously treated for atherosclerotic disease by balloon angioplasty or any of the other primary treatment modalities described above. The present invention, however, is further suitable for treating other hyperplastic and neoplastic conditions in other body lumens, such as the ureter, the biliary duct, respiratory passages, the pancreatic duct, the lymphatic duct, and the like. Neoplastic cell growth will often occur as a result of a tumor surrounding and intruding into a body lumen. Inhibition of such excessive cell growth is necessary to maintain patency of the lumen.
Treatment according to the present invention is effected by cooling target tissue to a temperature which is sufficiently low for a time which is sufficiently long to inhibit excessive cell proliferation. The cooling treatment will be directed against all or a portion of a circumferential surface of the body lumen, and will preferably result in cell growth inhibition, but not necessarily in significant cell necrosis. Particularly in the treatment of arteries following balloon angioplasty, cell necrosis may be undesirable if it increases the hyperplastic response. Thus, the present invention will slow or stop cell proliferation but may leave the cells which line the body lumen viable, thus lessening hyperplasia.
Methods according to the present invention comprise cooling an inner surface of the body lumen to a temperature and for a time sufficient to inhibit subsequent cell growth. Generally, the temperature at the tissue surface will be in a range from about 0xc2x0 C. to about xe2x88x9280xc2x0 C., the tissue surface temperature preferably being in a range from about xe2x88x9210xc2x0 C. to about xe2x88x9240xc2x0 C. In other embodiments, the temperature at the cell surface can be in the range from xe2x88x9220xc2x0 C. to xe2x88x9280xc2x0 C., optionally being from xe2x88x9230xc2x0 C. to xe2x88x9250xc2x0 C. The tissue is typically maintained at the described temperature for a time period in the range from about 1 to about 60 seconds, often being from 1 second to 10 seconds, preferably from 2 seconds to 5 seconds. Hyperplasia inhibiting efficacy may be enhanced by repeating cooling in cycles, typically with from about 1 to 5 cycles, with the cycles being repeated at a rate of about one cycle every 60 seconds. In the case of arteries, the cooling treatment will usually be effected very shortly after angioplasty, arthrectomy, rotational arthrectomy, laser angioplasty, stenting, or another primary treatment procedure, preferably within one hour of the primary treatment, more preferably within thirty minutes within the primary treatment, and most preferably immediately following the primary treatment.
The methods of the present invention may be performed with cryosurgical catheters comprising a catheter body having a proximal end, a distal end, and a primary lumen therethrough. The primary lumen terminates in a Joule-Thomson orifice at or near its distal end, and a balloon is disposed over the orifice on the catheter body to contain a cryogenic fluid delivered through the primary lumen. Suitable cryogenic fluids will be non-toxic and include liquid nitrogen, liquid nitrous oxide, liquid carbon dioxide, and the like. By delivering the cryogenic fluid through the catheter body, the balloon can be expanded and cooled in order to effect treatments according to the present invention.
Preferably, the Joule-Thomson orifice will be spaced inwardly from each end of the balloon and the balloon will be sufficiently long so that the cooling of the balloon occurs primarily in the middle. The temperature of the proximal and distal ends of the balloon will thus be much less than that of the middle, and the ends will thus act as xe2x80x9cinsulatingxe2x80x9d regions which protect luminal surfaces and other body structures from unintended cooling. Preferably, the balloon has a length of at least 1 cm, more preferably at least 2 cm, and typically in the range from 3 cm to 10 cm. The orifice is usually positioned at least 0.5 cm from each end, preferably being at least 1 cm from each end in balloons which are 2 cm or longer.
While it has been found that positioning of the Joule-Thomson valve in the central region of a balloon will usually provide sufficient insulation of each end resulting from the inherent heat transfer characteristics, in some instances it will be desirable to provide a separate containment bladder nested inside the balloon to receive the cryogenic fluid. The containment bladder will further act to limit cooling to the central region of the balloon. The portions of the balloon proximal and distal to the containment bladder may optionally be inflated with an insulating medium, such as a gas, silicone oil, saline, or the like. Alternatively, the containment bladder may have a vent or be partially porous so that the cryogenic fluid (which is present as a gas within the containment bladder) flows at a controlled rate into the overlying balloon. By limiting the flow rate, the temperature of the cryogenic fluid will be significantly higher in the regions outside of the containment bladder but still within the balloon.
In another aspect, the present invention provides a cryosurgical system comprising a flexible catheter body having a proximal end, a distal end, and a gas exhaust lumen defining an axis therebetween. An intravascular balloon is disposed near the distal end of the catheter body in fluid communication with the exhaust lumen. The balloon is expandable to radially engage a surrounding vessel wall. A cryogenic cooling fluid supply is in fluid communication with at least one port disposed within the balloon.
As described above, the at least one port may optionally comprise a Joule Thompson orifice. Alternatively, the at least one port may pass some or all of the cryogenic cooling fluid as a liquid. In fact, a plurality of ports may spray the fluid radially, the liquid in some cases distributed substantially uniformly over an inner surface of the balloon wall so that enthalpy of vaporization of the liquid cools a region of the balloon wall. The vaporization of the liquid will help to inflate the balloon, while the exhaust lumen limits pressure within the balloon to safe levels.
In another aspect, the invention provides a cryosurgical catheter for use in a blood vessel having a vessel wall. The cryosurgical catheter comprises a flexible catheter body having a proximal end, a distal end, and a gas exhaust lumen defining an axis therebetween. A balloon is disposed at the distal end of the catheter body in fluid communication with the exhaust lumen. The balloon has a balloon wall with proximal and distal ends and a radially oriented region extending therebetween. The wall is radially expandable to engage the surrounding vessel wall. At least one cooling fluid distribution port is in communication with a cryogenic cooling fluid supply. The at least one port is disposed within the balloon to cool the region of the expanded balloon wall.
The cryosurgical methods and catheters of the present invention will often be tailored to provide even cooling along at least a portion of a vascular wall engaged by the cooled balloon. For example, the efficacy of cryogenic cell growth inhibition may be enhanced significantly by distributing cooling within the balloon using a plurality of cryogenic fluid ports distributed circumferentially and/or axially within the balloon so that a significant portion of the vessel wall engaging the balloon surface is cooled to the target temperature range for a time in the desired treatment period range.
In this aspect, the present invention provides a cryosurgical catheter for use in a blood vessel having a vessel wall. The cryosurgical catheter comprises a flexible catheter body having a proximal end, a distal end, and a lumen defining an axis therebetween. A balloon is disposed at the distal end of the catheter body. The balloon is in fluid communication with the lumen, and has a balloon wall that expands radially to engage the surrounding vessel wall. A plurality of cooling fluid distribution ports are in communication with a cooling fluid supply. These ports are distributed within the balloon so as to evenly cool a portion of the vessel wall.
To maximize cooling efficiency and minimize gas pressure within the balloon, it is generally preferable to minimize the total cooling fluid flow out of the exhaust lumen from the balloon. Efficiency can also be enhanced by directing the cooling fluid radially against the balloon wall, ideally using a plurality of ports that are separated circumferentially about a diffuser head. When treating long diseased segments of the vasculature, for example, when treating hyperplasia of the iliac or superior femoral arteries, it would be beneficial to treat the entire segment without moving or repositioning the balloon. To provide even treatment within such an elongated diseased vessel, the diffuser head may be moved axially within the inflated balloon by sliding a cooling fluid supply tube axially within the catheter body. Such a structure may provide a variety of controllable sequential cryogenic treatment regimens, for example, multiple temperature feedback controlled cryogenic treatment cycles for inhibiting cell proliferation, or for a variety of alternative endoluminal cryogenic therapies. Alternatively, a fixed diffuser head defining an axially and circumferential distributed array of ports may provide simultaneous even cooling throughout a significant region of the target site.
In a related method aspect, the invention provides a therapy for treatment of a blood vessel having a vessel wall. The method comprises introducing a catheter into the blood vessel, and expanding a balloon of the catheter near a target site to engage the vessel wall. Fluid is expanded at a first location within the balloon. Fluid is also expanded at a second location within the balloon to cryogenically cool a portion of the engaged vessel wall, the second location being separated from the first location.
Gas expansion may effect cryogenic cooling via Joule-Thompson expansion as the cryogenic fluid enters the balloon and/or via the enthalpy of vaporization of a cryogenic fluid within the balloon. There may be significant temperature transients when cryogenic cooling is first initiated from within the balloon catheter. To enhance the surgeon""s control over the cooling rate and treatment time of these cryogenic therapies, gas expansion may be initiated while a moveable orifice head is disposed within a housing or shield at one end of the balloon. This housing may conveniently be formed by extending a tubular structure distally from the catheter body into the interior of the balloon. Such a housing structure may also be used to help direct exhaust gases proximally out of the balloon without causing excessive cooling at the proximal end of the balloon, which exhaust gases might otherwise freeze blood within the vessel.
In yet another aspect, the invention also provides a kit for treating hyperplasia or neoplasia in a body lumen. The kit comprises a catheter having a proximal end, a distal end, and balloon near its distal end. Instructions are included in the kit for use of the catheter. These instructions comprise the step of cooling an inner surface of the body lumen with the balloon to a temperature and for a time sufficient to inhibit subsequent cell growth. Such a kit may include instructions for any of the methods described herein.